Animal Models and Hormone Replacement Therapy

I do not usually comment on the use of animal products in medical treatments (some work, some don’t) but hormone replacement therapy (HRT) is again in the news so I thought I should comment on the parallels between the HRT fiasco and what I usually discuss: animal models used for predictive purposes.

A new UCSF study of 700,000 women published in theJournal of Clinical Oncology revealed an association between a decrease in the use of hormone replacement therapy and a reduction in breast cancer. This is yet more evidence that HRT like Prempro caused breast cancer and should be avoided. The well-known Prempro study was halted early in 2002 showed when it revealed an increase risk of breast cancers, heart attacks and strokes. Another study was halted was in 2004 when Premarin was linked to an increase risk of strokes. Prempro has also been linked to an increased risk for dementia, an increased death rate in women with lung cancer, and an increased risk of kidney stones.

Karla Kerlikowske, MD, coauthor of the study and professor of medicine, and epidemiology and biostatistics at the UCSF Helen Diller Family Comprehensive Cancer Center, and co-director of the Women Veteran's Comprehensive Health Center at SFVAMC:

We show that the incidence of breast cancer decreases if you take the hormones away. The fact that we're continuing to see a decrease in invasive cancer means that the effects of stopping the hormones may be long-lasting . . . The study supports the idea that by giving the hormones we were promoting tumor growths by giving the hormones . . . When the promoter is taken away, the incidence of breast cancer decreases.

What role did animal models play in starting HRT in the first place? Rothwell:

Prediction of the clinical consequences of interventions based on their effects in model systems has also often proved difficult. For example, the contrast between the countless reports of apparently beneficial effects of oestrogens on vascular biology in the laboratory and the harm later seen in large randomised trials of hormone replacement therapy is by no means atypical. (Rothwell 2006)

Science:

In mice and monkeys it [HRT] works wonders for the heart, but in a study of thousands of women it falls flat. (Couzin 2003)

US News:

Marcia Stefanick knows she will not get through this October day without hearing about monkeys. The Stanford University medical professor is addressing a major meeting of researchers and physicians at the National Institutes of Health, detailing the recent results of what everyone calls simply "The Study." The Study is part of the massive Women's Health Initiative, and the findings are not good news. The hoped-for health benefits of hormone replacement therapy, known universally as HRT, are not turning up. "It's clear now that there is no cardiovascular benefit," she tells her audience.

A physician approaches the microphone. He has a bone to pick: "In the monkey trials," he says, "hormones reduce heart risk and atherosclerosis if the monkeys are started on hormones early enough. Don't you think you would have found long-term benefits if the women in the trial had been younger and started hormones earlier? Are you aware of the monkey data?" Stefanick, who has worked on most of the recent hormone trials, is struggling to conceal her annoyance. "Yes, I'm familiar with the monkey data," she says evenly. She once again goes over her newest analysis of the WHI results, showing that younger women had more risks and fewer benefits than the average women in The Study. "We've got to get our arms around this: HRT does not provide cardiovascular protection. We were wrong. We were just wrong" . . .

Elias Zerhouni, the director of NIH, captured the current state of the hormone debate when he said, "Often in science the reaction to a new finding is directly proportional to the strength of the dogma it overturns. People are still in denial of the theory of relativity, too." (Spake 2004) (Emphasis added.)

When birth control pills first were introduced, no one suspected the side effect of blood clots. Extensive animal tests had revealed no such problem. In fact, dogs had predicted that the pill would actually decrease the likelihood of clotting (Bankowski and Howard-Jones 1984). Of course, we now know that certain people can develop life threatening blood clots when taking the pill. Scientists have said the following about the animal studies of birth control pills:

[Of] the conditions in humans associated epidemiologically with an increased risk in pill users . . . none . . . was predicted by toxicity tests in experimental animals… The increase risk of thromboembolic disorders [stroke], which is primarily associated with the estrogen component of the pill, has no analogue in animals. Changes in blood coagulation parameters have only been observed in dogs, but in them they have been due to a specific progestin-related increase in plasma fibrinogen . . . It is apparent that most of the salient findings in animal experiments have lacked analogues in humans, and most of the adverse and beneficial effects associated with the use of contraceptives have not been predicted by toxicity tests [(Lehman 1989) p52-79].

Gunzel et al: 1989:

Monkeys regulate pregnancy at a significantly lower progesterone level than all other experimental animal species. Only humans show a dramatic increase during the last third of gestation [pregnancy] . . . No animal species has yet been identified that invariably has the same protein binding pattern [of sex hormones] as man. [(Gunzel 1989) p19-49]

I am sure some vivisection activist will point out that hormones or some specific hormone was first discovered in an animal. My issue is not that animals have been used in the past to discover the commonalities of life. They have. Hormones per se could have been discovered in humans (and maybe they were, I simply do not know the history of hormone discovery) or in animals. The issue I am raising revolves around the ubiquitous practice of using animal models to predict human response to drugs and disease and the even more ubiquitous practice of selling animal use in general to society based on this myth. HRT, and the deaths it caused, is just one more example of the results of believing this myth.